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BIG PHYSICS, BIG QUESTIONS –

Why the search for smart genes is doomed

By Bob Holmes

RANSACKING the human genome in search of genes that determine intelligence is a fool’s errand, a geneticist told the AAAS last week. The influences of nature and nurture are too closely intertwined for researchers to separate them cleanly, said Douglas Wahlsten, a behavioural geneticist at the University of Alberta in Edmonton, Canada. And the influence of any single gene is almost certainly small, so researchers would need to study huge numbers of people to show convincing proof of its role.

Support for Wahlsten’s view came from Peter Schöneman of Purdue University, Indiana, who argued that even the concept of intelligence is difficult to define. Most psychologists now believe that there is no single, underlying ability called “intelligence”. Instead, they say people display different abilities for different kinds of thinking. “People don’t know what intelligence is any more than they did in the 1930s,” said Schöneman. “So how can you talk about how it is inherited?”

Even if researchers can agree on a measure of intelligence, such as a standardised IQ test, said Wahlsten, identifying a gene’s effects is fraught with methodological problems. In a general population, most IQ tests yield a roughly bell-shaped distribution of IQs, usually a sign that many genes with small effects are combining to determine the outcome.

But the smaller a gene’s effect, the harder geneticists have to look to find it. To be confident of detecting an IQ difference of 3 points between two groups of people, for example, researchers would need more than 500 individuals in each group.

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A gene’s effect may also depend on its environmental context. One gene, for example, might make a child’s mental development more sensitive to malnutrition. A child with such a gene would be slower than his or her classmates if poorly nourished, but would not stand out if well fed.

Researchers who think they have found a gene that affects intelligence will need to understand the influence of diet, family environment and other environmental factors. “Then, maybe, we can help someone with that knowledge,” Wahlsten said. “The way they’re going right now, they’ll just be able to say that here’s a gene that affects IQ.” Unfortunately, he said, to achieve this deeper understanding would need sample sizes of 4000 or more.

And the problems do not end there. Members of different ethnic groups may differ genetically, but their diets, child-rearing practices, and many other cultural features also differ. Amid such a jumble, said Wahlsten, “no sample size in the world can tease apart the possible causes” of variations in IQ. Even differences in IQ between adopted and biological children brought up by the same parents – where the only distinction might appear to be the genetic origin of the children – need not be caused by genes, since the children will have experienced different environments during gestation and immediately after birth.

Wahlsten also pointed to problems in a popular DNA technique for separating genetic from environmental influences. Geneticists have identified several thousand short stretches of variable DNA scattered throughout the genome which they can use as markers for possible intelligence genes. They study whether brighter people are more likely to have a particular form of one of these markers. If so, then a gene that alters intelligence probably lies close to the marker on the same chromosome.

But with thousands of markers to search, geneticists risk finding false positives – markers that, just by chance, happen to vary in the population in the same way as intelligence. The history of behavioural genetics is littered with such cases. Geneticists have announced the discovery of genes for alcoholism, manic depression and even divorce, only to retract their claims later.

To guard against false positives, statisticians advise using much more stringent standards of proof on these fishing expeditions in the gene pool. But that means researchers will need to increase their sample sizes still further.

With all these problems to confront, said Wahlsten, proving how genes affect intelligence will be much harder than most geneticists realise – possibly as much effort as putting a man on the Moon. “Personally,” he said, “I think it would be a squandering of taxpayers’ money.”